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Ketone Body β-hydroxybutyrate Inhibits Inflammation to Reduce Alzheimer's Pathology in a Mouse Model


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Posted 01 October 2020 - 10:11 AM


Ketosis is a response to low dietary intake of carbohydrates, and one of the mechanisms by which calorie restriction produces benefits to health and longevity. A ketogenic diet attempts to capture that part of the process by reducing carbohydrate intake without reducing calorie intake. Ketosis results in the production of ketone bodies, metabolites that change cellular behavior for the better throughout the body. One beneficial effect is a reduction in chronic inflammation, via inhibition of the inflammasome as shown here. The sustained inflammation of aging is important in the progression of neurodegenerative conditions such as Alzheimer's disease, and, as demonstrated here, suppression of inflammation improves matters in a mouse model of the condition.

Alzheimer's disease (AD) is a progressive, late-onset dementia with no effective treatment available. Recent studies suggest that AD pathology is driven by age-related changes in metabolism. Alterations in metabolism, such as placing patients on a ketogenic diet, can alter cognition by an unknown mechanism. One of the ketone bodies produced as a result of ketogenesis, β-hydroxybutyrate (BHB), is known to inhibit NLRP3 inflammasome activation. Therefore, we tested if BHB inhibition of the NLRP3 inflammasome reduces overall AD pathology in the 5XFAD mouse model of AD.

Here, we find BHB levels are lower in red blood cells and brain parenchyma of AD patients when compared with non-AD controls. Furthermore, exogenous BHB administration reduced plaque formation, microgliosis, PYCARD speck formation, and caspase-1 activation in the 5XFAD mouse model of AD. Taken together, our findings demonstrate that BHB reduces AD pathology by inhibiting NLRP3 inflammasome activation. Additionally, our data suggest dietary or pharmacological approaches to increase BHB levels as promising therapeutic strategies for AD.

Link: https://doi.org/10.1...974-020-01948-5


View the full article at FightAging




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